What is the diagnostic approach for brucellosis in pediatric patients?

Diagnosis of Brucellosis in Children

Brucellosis diagnosis in children requires obtaining blood cultures (2 sets) combined with serological testing using standard tube agglutination (STA), with titers ≥1:160 considered diagnostic when paired with compatible clinical presentation. 1

Clinical Suspicion and Risk Assessment

Suspect brucellosis in children presenting with:

• Fever (present in all cases) with epidemiologic risk factors including consumption of unpasteurized dairy products, occupational/household exposure to livestock, or residence in endemic areas 1, 2, 3
• Subacute presentations with low-grade relapsing or irregular fever patterns, lymphadenopathy, hepatosplenomegaly, or osteoarticular complaints 1, 2
• Nonspecific systemic symptoms including malaise, anorexia, sweating, weight loss, and joint pain 3, 4
• Returned travelers from endemic regions presenting with fever of unknown origin 1

Diagnostic Testing Algorithm

Primary Diagnostic Tests

Blood cultures are essential and must be obtained in all suspected cases:

• Collect 2 sets of blood cultures with sensitivity ranging 15-70% depending on laboratory practices 1
• Critical safety consideration: Discuss blood culture requests with the laboratory beforehand, as initial processing requires biosafety level 3 precautions due to aerosolized transmission risk to laboratory workers 1
• Cultures require prolonged incubation up to 4 weeks 1

Serological testing using standard tube agglutination (STA):

• Titers ≥1:160 are considered diagnostic when combined with compatible clinical presentation 1, 3
• The Brucella Coombs gel test is widely used, with higher titers (≥1/640) significantly associated with complicated disease including bone-joint involvement 2
• Positive serology was documented in the majority of pediatric cases 3, 4

When Blood Cultures Are Negative

Bone marrow culture has the highest sensitivity and is the investigation of choice when blood cultures remain negative despite high clinical suspicion. 1

Baseline Laboratory Markers

Obtain the following to support diagnosis and assess complications:

• Inflammatory markers: ESR and CRP, as elevated levels correlate with complicated brucellosis including bone-joint involvement and organomegaly 2
• Complete blood count: Anemia (35.6%), leukopenia (9.9%), thrombocytopenia (3.9%), and pancytopenia (13.3%) are commonly observed 2, 4
• Liver function tests: At least one elevation in LFT results occurs in approximately 31.7% of pediatric patients 2

Special Diagnostic Considerations

Bone-Joint Involvement

For suspected brucellar vertebral osteomyelitis or osteoarticular disease:

• MRI of the spine is the imaging modality of choice with 97% sensitivity and 93% specificity 1
• In endemic settings with suspected vertebral osteomyelitis, strongly positive Brucella serology (≥1:160) combined with compatible imaging obviates the need for image-guided biopsy 1
• High Brucella CT titers (≥1/640) and increased ESR are significantly associated with bone-joint brucellosis 2

Neurobrucellosis

• Cerebrospinal fluid analysis should be performed when neurological symptoms are present, showing elevated white blood cells, elevated protein, and decreased glucose 5
• Metagenomic next-generation sequencing (mNGS) of CSF can provide early diagnostic utility in neurobrucellosis, particularly in non-endemic areas where the diagnosis may be overlooked 5

Common Diagnostic Pitfalls

• Nonspecific presentation: Brucellosis mimics many other diseases, making diagnosis difficult in pediatric patients; maintain high index of suspicion with appropriate epidemiologic risk factors 2, 3
• Laboratory safety: Failure to notify laboratory of suspected brucellosis creates significant occupational hazard for laboratory workers 1
• Premature diagnostic closure: The variety of clinical manifestations (fever, cytopenia, elevated LFTs, organomegaly) requires considering brucellosis in the differential diagnosis of multiple pediatric syndromes 2, 4
• Inadequate culture incubation: Blood cultures require prolonged incubation up to 4 weeks; premature reporting as negative may miss diagnosis 1